Thrombospondin-4 regulates apoptosis of vascular smooth muscle cells after artery transplanted into vein.

The molecular mechanism of vascular atrophy and remodeling after arterial transplantation into a venous environment remains unclear. This study grafted the common carotid artery of New Zealand white rabbits into the external jugular vein to establish an animal model of arterial mechanical unloading. Its efficacy was verified by ultrasound. Immunohistochemical methodologies, transmission electron microscopy, and TUNEL staining showed vascular morphology changes. Genomic analysis, proteomic profiling, iPathway guide (IPG) analysis, gene overexpression/silenced, flow cytometry, and stretch testing were applied to elucidate the molecular mechanisms. Comparative analysis between the arterial graft and the control group revealed the successful preparation of the animal model in vitro. Morphological examination indicated that atrophy under venous flow mechanics is predominantly attributed to the apoptosis of vascular smooth muscle cells (VSMCs). Bioinformatics results proved that thrombospondin-4 (THBS4) plays a pivotal role in vascular remodeling via the focal adhesion pathway. Experiments demonstrated THBS4's regulation of VSMCs apoptosis and its relation with low stretch tension. This study was the first to introduce gene transcriptomics and proteomics into the arterial mechanical unloading animal model and the first to demonstrate the role of THBS4 in promoting VSMCs apoptosis. Consequently, THBS4 emerges as a promising therapeutic target for the prevention of intimal hyperplasia post-vascular transplantation in vascular surgery.